Concomitant schistosomiasis and HCV infection is common in Egypt and many developing countries and represents a major health problem. The majority of patients with concomitant HCV and schistosomiasis fail to clear HCV infection and progress to chronic hepatitis C with a severe clinical course, higher HCV RNA titers, higher incidence of cirrhosis and, hepatocellular carcinoma, poor response to interferon therapy and higher mortality rates due to liver related causes when compared to patients infected with HCV alone. The mechanisms of HCV and Schistosoma mansoni interactions and the immunological changes that occur during such a co-infection are to date not clearly defined due to the absence of a small animal model that can support both infections. However, the difference in the outcome and rate of progression of HCV infection during concomitant hepatic schistosomiasis suggest that such parasitic-viral interaction may account for the modulation of natural course of both infections. This pattern of viral/parasitic co-infection offers a unique opportunity to study the evolution and kinetics of human immune responses towards HCV in a setting of prevailing T-helper 2 immune response. In the proposed prospective study it is hypothesized that co-infection with S. mansoni may decrease the effective immunity in HCV infection through inadequate T helper cell responses and immune escape from CTL recognition. The proposed prospective study will characterize the kinetics of HCV specific CTL and T helper cell responses in a unique cohort of patients with acute hepatitis C without and with Schistosoma mansoni co-infection matched for age, gender, HCV genotype and HLA phenotypes. The immune parameters will be correlated to the clinical outcome and progression of HCV infection to determine the correlates of immune protection in this infection. In the proposed study, novel and highly sensitive immunologic assays, including Elispot and flow based tetramer and intracellular cytokine assays will be used, to perform a detailed characterization of the immune response to HCV in acute and chronic infection. In addition special focus will be directed to investigating the intrahepatic immunological parameters in persons who do not control viremia. It is anticipated that investigating this pattern of viral-parasitic interaction will projects will provide useful information for development of more effective diagnostic, prevention and treatment strategies.